Phosphorylation of Amino(aryl)methylphosphonates by the Atherton—Todd Reaction

Abstract

SHORT COMMUNICATIONSAmong amidophosphate derivatives, promising are N-(α-phosphoryl)amidophosphates possessing two four-coordinate phosphorus atoms. These organophosphorus compounds exhibit biological activity and are used as chelating ligands for complex formation with some metal ions [1,2]. They are usually synthesized by phosphorylation of amino phosphonates with diethyl chlorophosphate [3].We were the first to perform phosphorylation of amino(aryl)methylphosphonates having a primary amino group under the Atherton-Todd reaction conditions. The reactions of amino(aryl)methylphosphonates Ia-Ie with diethyl phosphonate and carbon tetrachloride in the presence of triethylamine were carried out at room temperature, on heating at 110ºC, and under microwave irradiation. The reactions under microwave irradiation were complete in 30-40 min, and the corresponding N-(α-phosphoryl)amidophosphates IIa-IIe were obtained in 63-93% yield. No reaction occurred at room temperature, whereas after heating for 24 h at 110°C compounds IIa-IIe were isolated in poor yields (15-20%) due to predominant formation of pyrophosphate on prolonged heating.The product structure was confirmed by their 1 H, 13 C, and 31 P NMR spectra and elemental analyses. Compounds IIa-IIe displayed in the 31 P NMR spectra doublet signals at δ P 6.2-6.8 and 22.2-22.6 ppm with coupling constants of 40.2-42.7 Hz. In the 1 H NMR spectra of IIa-IIe, the NCH proton characteristically resonated at δ 4.4-4.6 ppm, and the corresponding carbon signal appeared in the 13 C NMR spectra as a doublet at δ C 51.3-53.8 ppm (J PC = 153-156 Hz). Diethyl aryl(diethoxyphosphorylamino)methylphosphonates IIa-IIe (general procedure).Carbon tetrachloride, 20 mmol (3.08 g, 2.11 ml), triethylamine, 15 mmol (1.52 g, 1.08 ml), and aminophosphonate Ia-Ie, 10 mmol, were added in succession to 10 mmol (1.38 g, 1.29 ml) of diethyl phosphonate. The reaction was carried out in an open vessel under microwave irradiation (102 W, 115°C). The precipitate of triethylamine hydrochloride was filtered through a glass filter, the filtrate was cooled and evaporated on a rotary evaporator, and the residue was subjected to column chromatography on silica gel using chloroform-methanol (50 : 1) as eluent. Diethyl α-[(diethoxyphosphoryl)amino]benzylphosphonate (IIa). Reaction time 40 min. Yield 3.22 g (85%), oily substance. 31 P NMR spectrum (CDCl 3 ), δ P , ppm: 6.78 d and 22.20 d ( 3 J PP = 41.3 Hz) [3].Diethyl α-[(diethoxyphosphoryl)amino]-4-methylbenzylphosphonate (IIb). Reaction time 35 min. Yield 3.46 g (88%), oily substance. 1 H NMR spectrum (CDCl 3 ), δ, ppm: 1.06 t (3H, CH 3 CH 2 OPNH, 3 J = 7.2 Hz), 1.12 t (3H, CH 3 CH 2 OPNH, 3 J = 7.2 Hz), 1.27 t (3H, CH 3 CH 2 OPCH, 3 J = 6.8 Hz), 1.33 t (3H, CH 3 CH 2 OPCH, 3 J = 6.8 Hz), 1.88 br.s (1H, NH), 2.19 s (3H, CH 3 C 6 H 4 ), 3.65-3.70 m (2H, NHPOCH 2 ), R = Ph (a), 4

Atherton–Todd reaction: mechanism, scope and applications

“…AT reactions usually proceed at 0–5 °C but lower temperatures (−10 °C [ 41 ]) and higher temperatures (50°C [ 76 ]) were also reported. The use of microwave (MW) activation was also reported by Beletskaya et al [ 79 ]. This activation was applied to AT reactions which used α-aminophosphonate as a nucleophile in the presence of CCl 4 and triethylamine.…”

“…The use of microwave (MW) activation was also reported by Beletskaya et al [79]. This activation was applied to AT reactions which used α-aminophosphonate as a nucleophile in the presence of CCl 4 and triethylamine.…”

Double Hydrophosphorylation of Nitriles Catalyzed by Rare-Earth-Metal Lanthanum

“…This compound is known in the literature. 11,20 Diethyl ((4-Bromophenyl)(diethoxyphosphoryl)methyl)phosphoramidate (3b):…”

A rhodamine-phosphonate off–on fluorescent sensor for Hg2+ in natural water and its application in live cell imaging

“…Compound 3 was synthesized by a similar way described in a reported method [17]. The concrete way was described as follows:…”